Is CARD14 p.Phe492= (c.1476C>T) pathogenic?

CARD14 p.Phe492= (c.1476C>T) is classified Benign/Likely benign in CARD14 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.54%, afr); Associated with pityriasis rubra pilaris.

What condition is associated with CARD14 p.Phe492= (c.1476C>T)?

CARD14 p.Phe492= (c.1476C>T) is associated with pityriasis rubra pilaris, psoriasis 2, autoinflammatory syndrome (ClinVar).

How common is CARD14 p.Phe492= (c.1476C>T) in the general population?

CARD14 p.Phe492= (c.1476C>T) is low-frequency (popmax 1.54%, afr) (gnomAD).

CARD14 p.Phe492=

c.1476C>T · rs144710573 · VCV527889

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, afr)

Conditions

pityriasis rubra pilaris

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -2.7, phastCons 0.017
Overall
CADD	8.809	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.54% African / African-American · 1,158/75,022 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.109% 1,763/1,612,350 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.54%	65
South Asian	0.29%	345
Admixed American	0.147%	681
Remaining individualsnot grpmax-eligible	0.144%	694
Middle Eastern	0.0992%	1,008
European (non-Finnish)	0.0127%	7,862
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,859
East Asian	0.00446%	22,421
Finnishnot grpmax-eligible	0.00316%	31,633

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CARD14
Protein: p.Phe492=
Coding: c.1476C>T
MANE Select: NM_001366385
dbSNP: rs144710573
Type: single nucleotide variant
Location: chr17:80195310 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.89
Residue 492: the 'maintains the protein in an inactive state' region

Full CARD14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pityriasis rubra pilaris — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: psoriasis 2 autoinflammatory syndrome

Similar variants

CARD14 p.Phe492Cys Uncertain significance ★ ⚠ same residue
CARD14 p.Phe492Val Uncertain significance ★ ⚠ same residue
CARD14 c.349+1G>A Pathogenic ★★ same condition
CARD14 p.Leu156Pro Pathogenic/Likely pathogenic ★★ same condition
CARD14 p.Met119Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CARD14 c.1089+5C>G Uncertain significance ★★ same condition
CARD14 c.1357-1G>A Uncertain significance ★★ same condition
CARD14 c.2569+2T>A Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/card14-p-phe492 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown